Article
Hematologic Complications in Patients Hospitalized with
COVID-19 Infection
Elisa Lin , Ellen Araj, John Markantonis, Hung Luu
Citation: Lin, E.; Araj, E.;
Markantonis, J.; Luu, H.; Chen, M.
Hematologic Complications in
Patients Hospitalized with COVID-19
Infection. Hematol. Rep. 2022, 14,
228–234. https://doi.org/10.3390/
hematolrep14030031
Academic Editor: Claudio Cerchione
Received: 7 May 2022
Accepted: 4 July 2022
Published: 11 July 2022
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Hematol. Rep. 2022, 14, 228–234. https://doi.org/10.3390/hematolrep14030031
and Mingyi Chen *
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75019, USA;
elisa.lin@utsw.edu (E.L.); ellen.araj@utsw.edu (E.A.); john.markantonis@utsw.edu (J.M.);
hung.luu@utsw.edu (H.L.)
* Correspondence: mingyi.chen@utsw.edu; Tel.: +1-214-648-4791
Abstract: Introduction: This review summarizes data from patients with COVID-19 requiring in-
tensive care unit (ICU) admission. The goals of this study are to showcase some morphological
anomalies found in peripheral blood smears from COVID-19 patients and to bring attention to how
some hematologic abnormalities in COVID-19 that correspond to disease severity and mortality.
Methods: We performed a retrospective analysis of hematologic parameters using peripheral blood
smear analysis from 31 COVID-19 patients hospitalized between April 2021 and January 2022. Results:
We found abnormal morphology that has not been previously reported. We also report that severe
lymphopenia, neutrophilia, acute hemolysis, hematologic malignancies, and increased LDH are
associated with ICU admissions, respiratory failure requiring intubation, and poor clinical outcome.
Conclusion: We propose these recommendations in the management of COVID-19 patients: 1. Early
diagnosis and follow-up of DIC; 2. Optimization of thromboprophylaxis regimen.
Keywords: COVID-19; hematology; complications; hemolysis
1. Introduction
Coronavirus disease 2019 (COVID-19) manifests with a wide range of symptoms, from
asymptomatic to fatal [1]. Although COVID-19 has been well-studied and characterized,
the pathophysiology underlying disease severity and progression remains unclear [1].
Although COVID-19 is primarily a disease of the lower respiratory tract, we now know
that it can affect a wide range of systems in the body, including the hematologic system [2].
However, there is conflicting evidence regarding the correlation between the severity of
COVID-19 disease and lymphopenia, neutrophilia, and thrombocytopenia; lymphocytosis
and neutropenia have been reported in 22% of 486 hospitalized children and 16.7% of
pregnant women, respectively, and prevalence of thrombocytopenia varies from 5 to 41.7%
in COVID-19 patients [2–5].
In the hematologic system, it is known that SARS-CoV-2 infects monocytes and en-
dothelial cells, which can result in a cytokine storm-like event and downstream intravascu-
lar thrombosis [3]. While arterial and venous thromboses have been reported in patients
with COVID-19, DIC is less commonly reported [3,6]. Increased levels of biomarkers
such as LDH, D-dimer, ferritin, and C-reactive protein have been studied and have been
shown to be associated with poorer outcomes in COVID-19 patients [7,8]. Morphological
abnormalities in COVID-19 patients that have been noted include C-shaped, single-lobed
neutrophil nuclei, blue-green leukocyte inclusions in circulating neutrophils and/or mono-
cytes, hyperchromatic platelets, and apoptotic and immature granulocytes [7,8].
In this study, we aim to review morphological and hematological abnormalities in
patients with COVID-19 requiring intensive care unit (ICU) admission and intubation, and
to bring attention to the biomarkers and abnormalities that should lead to change in patient
care. We highlight several cases with significant complications impacting the hematopoietic
system and hemostasis.
https://www.mdpi.com/journal/hematolrep
Hematol. Rep. 2022, 14 229

2. Materials and Methods

Study Population
We performed a retrospective analysis of hematologic parameters of 31 hospitalized
COVID-19 patients from Clements University Hospital and Parkland Memorial Hospital
in Dallas, Texas, between April 2021 and January 2022. Laboratory data, clinical out-
comes, demographic data, and past medical history were obtained from electronic medical
records. Peripheral blood smears were made by dropping a small amount of the sample
and spreading on a glass slide, which was stained with Wright–Giemsa and examined
for cells with morphologic abnormalities. All patients had confirmed cases of COVID-19
by nucleic acid amplification tests (NAATs). The study included hospitalized COVID-19
patients with multiple complications and comorbidities, including renal failure, fulminant
liver failure, shock, ischemic colitis, bowel ischemia, renal transplant, methicillin-resistant
Staphylococcus aureus (MRSA) bacteremia, multisystem organ failure, multidrug-resistant
(MDR) Klebsiella, methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia, endocardi-
tis, severe pancreatitis, chronic hypoxemic respiratory failure, lung and liver transplant
due to idiopathic pulmonary fibrosis, type 2 diabetes mellitus, essential hypertension,
acute kidney injury, morbid obesity, human immunodeficiency virus (HIV), end stage renal
disease status post renal transplant, chronic histoplasmosis, cervical cancer, urinary tract
infection (UTI), nonischemic cardiomyopathy, allograft dysfunction, secondary hypogam-
moglobulinemia secondary to immunosuppression, thrombotic thrombocytopenic purpura
(TTP) with splenectomy, prostate cancer, cystic fibrosis, sarcoidosis, asthma, sickle cell
anemia, pregnancy, and hematologic malignancies (HMs). Severity of disease was assessed
by requirement for ICU support, intubation, and outcome (deceased or recovered). IRB
approval was attained for this study.
The current study was based on our observations in a small number of cases in a single
institution. An ongoing study with multi-center collaboration will provide more insight
into the underlying clinico-biological correlation between severe COVID-19 infection and
hematological disease.

3. Results
3.1. Morphological Anomalies in Peripheral Blood Smears from COVID-19 Patients
The morphological abnormalities we found included nuclear and cytoplasmic gran-
ulations (Figures 1 and 2). In particular, we observed many crowded, dark granulations
in the cytoplasm (similar to “toxic” granules) and peripheral light blue agranular areas
(Figures 1 and 2). A few cases had many hypogranular cells (Figure 1). The abnormalities
in nuclear shape included increased frequency, not only of band forms, but also dysmor-
phic cells with the total absence of nuclear segmentation, consistent with pseudo-Pelger
morphology (Figure 2).
Apoptotic cells were frequently found with either liquefied, granulated nuclear chro-
matin, or deep blue cytoplasm; they may have been derived from different cell types (i.e.,
neutrophils and lymphocytes, respectively). Immature granulocytes, especially small mye-
locytes and metamyelocytes, were also frequently present in early-phase cases, sometimes
with small azurophilic granules (Figure 1). Typical features included normocytic anemia
with increased polychromasia, circulating nucleated RBCs, basophilic stippling, left-shifted
granulocytes with toxic granulations, lymphopenia, and thrombocytopenia (Figure 1).
Hematol.
Hematol. Rep.
Rep. 2022,
2022, 14,
14, FOR
FOR PEER
PEER REVIEW
REVIEW 33
Hematol. Rep. 2022, 14 230

Figure1.
Figure
Figure Peripheralblood
1.1.Peripheral
Peripheral blood smear
blood smear analysis
smear analysis showing
showingincreased
showing increasedrouleaux
increased rouleauxformation,
rouleaux formation,
formation, normocytic
normocytic
normocytic anemia
ane-
ane-
withwith
mia
mia increased
with polychromasia,
increased
increased nucleated
polychromasia,
polychromasia, red blood
nucleated
nucleated red cells, cells,
red blood
blood basophilic stippling,
cells, basophilic
basophilic left-shifted
stippling,
stippling, granulocytes
left-shifted
left-shifted gran-
gran-
ulocytes
with toxic
ulocytes with toxic
toxic granulations,
granulations,
with lymphopenia,
lymphopenia,
granulations, and
and thrombocytopenia.
and thrombocytopenia.
lymphopenia, thrombocytopenia.

Figure 2.Peripheral
Figure 100× magnificationshowing
Peripheral smearatat100× showing a nucleatederythroid,
erythroid, a rareblast
blast with
Figure 2.
2. Peripheral smear
smear at 100× magnification
magnification showing aa nucleated
nucleated erythroid, aa rare
rare blast with
with
prominent
prominent nucleoli and immature chromatin pattern, a left-shifted myeloid series with immature
prominent nucleoli
nucleoli and
and immature
immature chromatin
chromatin pattern,
pattern, aa left-shifted
left-shifted myeloid
myeloid series
series with
with immature
immature
promyelocytesand
promyelocytes
promyelocytes andmetamyelocytes,
and metamyelocytes,and
metamyelocytes, andoccasional
and occasionalmonocytes.
occasional monocytes.
monocytes.

Peripheral blood
Apoptotic × magnification
smears at 100found often showed nucleated erythroids,
Apoptotic cells
cells were
were frequently
frequently found with
with either
either liquefied,
liquefied, granulated
granulated nuclear
nuclear chro-
chro-
rare
matin,blasts with prominent nucleoli and immature chromatin pattern, left-shifted myeloid
matin, or deep blue cytoplasm; they may have been derived from different cell types
or deep blue cytoplasm; they may have been derived from different cell types (i.e.,
(i.e.,
series with immature
neutrophils promyelocytes and metamyelocytes, and occasional monocytes
neutrophils and
and lymphocytes,
lymphocytes, respectively).
respectively). Immature
Immature granulocytes,
granulocytes, especially
especially small
small
(Figure 2).
myelocytes
myelocytes and
and metamyelocytes,
metamyelocytes, were
were also
also frequently
frequently present
present in
in early-phase
early-phase cases,
cases, some-
some-
times
times with
with small
small azurophilic
azurophilic granules
granules (Figure
(Figure 1).
1). Typical
Typical features
features included
included normocytic
normocytic
anemia
anemia with
with increased
increased polychromasia,
polychromasia, circulating
circulating nucleated
nucleated RBCs,
RBCs, basophilic
basophilic stippling,
stippling,
Hematol. Rep. 2022, 14 231

3.2. Hematologic Laboratory Abnormalities Correlate with Poor Clinical Outcome in

COVID-19 Disease
Of the 31 patients in the study, 6 patients were aged 19–30, 18 patients were aged
31–65, and 7 patients were aged 65 or above; 15 patients were Hispanic, 9 were black,
6 were non-Hispanic white, with data unavailable/unknown for 1 patient. Overall, 21 of
31 patients reviewed presented with severe dyspnea and high fever and were admitted
to the ICU after being confirmed positive for SARS-CoV-2. Some of the ICU patients (17)
developed severe hypoxic respiratory failure and were intubated. On admission, 15 patients
(48%) presented with lymphopenia (<1.3 × 109 /L) and occasional plasmacytoid reactive
lymphocytes; over the course of disease, all 15 experienced worsening lymphopenia.
Sixteen patients had absolute neutrophilia (>5 × 109 /L) trending downwards a week
thereafter (1.48–3.23 × 109 /L in seven followed-up cases) and left-shifted granulocytes. Six
patients had thrombocytopenia (<150,000/µL), however, three patients had thrombocytosis
(>450,000/µL). Further, 14 patients had a positive D-dimer (>0.5 mcg/mL), 9 patients had
high fibrinogen (>400 mg/dL), 9 patients had high PT (>14 s) while 3 had low PT (<10 s),
1 patient had INR greater than 3.5, and 7 patients had high PTT (>32.5 s) Eight patients
had HMs or were immunosuppressed on admission; five of them required ICU admission
and intubation, and ultimately passed away. It is noteworthy that the patients with
hematological malignancies such as lymphomas could have had longstanding lymphopenia
and elevated LDH prior to COVID-19 disease. Twenty-one patients had elevated LDH on
admission (>225 U/L); two had LDH greater than 1000 u/L (Table 1).

Table 1. Summary of results from laboratory tests and clinical outcomes.

Manifestation Number (%)

Severe dyspnea and high fever, admitted to ICU 21/31 (70%)
Severe hypoxic respiratory failure requiring intubation 17/21 (81%)
Lymphopenia (<1.3 × 109 /L) and occasional plasmacytoid reactive lymphocytes
15/31 (48%)
with exacerbation of lymphopenia over course of disease
Absolute neutrophilia (>5 × 109 /L) with left-shifted granulocytes 16/31 (52%)
Decreasing trend in subsequent week (1.48–3.23 × 109 /L) 7/16 (44%)
Hematologic malignancies or immunosuppressionICU admission and 8/31 (26%)
intubation, death 5/8 (63%)
Elevated LDH (>225 u/L) 21/31 (68%)
LDH > 1000 U/L 2/21 (10%)

4. Discussion
4.1. Hematologic Abnormalities in COVID-19 Are Related to Disease Progression, Severity,
and Mortality
Many cases of severe COVID-19 have been characterized by dysregulated inflamma-
tion and coagulation activation [2]. Pro-inflammatory cytokine secretion, microangiopathic
vasculopathy, and B-cell secretion of specific SARS-CoV-2 antibodies in infected cells are
induced by the SARS-CoV-2 S (spike) protein binding to ACE2 receptors in epithelial
cells of the respiratory tract [9]. In particular, COVID-19 disease with marked hematologic
abnormalities exhibit a characteristic pattern, similar to a “cytokine storm”, in which inflam-
matory markers and cytokines dramatically increase and significant lymphopenia develops.
Furthermore, hypercoagulability is common in hospitalized COVID-19 patients [6,10].
Coagulation abnormalities such as prolonged PT and PTT, increased fibrin degradation
products, and severe thrombocytopenia can lead to disseminated intravascular coagula-
tion (DIC), which is life-threatening and necessitates continuous vigilance and prompt
intervention [10–13]. Both thrombotic and hemorrhagic pathologies should be noted in
these patients, as well as macro- and microthrombosis [13]. Three mechanisms have been
proposed to lead to thrombocytopenia in COVID-19 patients. The first is a decrease in
platelet production due to myelosuppression either from SARS-CoV-2 or from therapy.
Hematol. Rep. 2022, 14 232

The second mechanism is direct platelet destruction by the immune system. The last
mechanism purports that platelet aggregration in the lungs results in microthrombi and
therefore platelet consumption [4,14]. However, thrombocytosis has also been recorded in
patients with COVID-19; it is proposed that some concurrent early-stage bacterial infections
may induce neutrophilia, left-shifted granulocytes, and secondary thrombocytosis [15].
Therefore, COVID diagnosis and disease severity must be determined early so extended
pharmacological thromboprophylaxis with low-molecular-weight heparin (LMWH) regi-
men can be started early in the disease course. By doing so, appropriate management can
be planned before at-risk patients develop organ failure or shock [2].

4.2. Lymphopenia in COVID-19

Lymphopenia in COVID-19 patients has been well documented. In Singapore, ap-
proximately 40% of the first 18 hospitalized patients with COVID-19 were found to have
lymphopenia [8]. More recently, a report on 69 COVID-19 patients confirmed that approx-
imately 40% of patients had lymphopenia, and 20% had mild thrombocytopenia [8]. Of
patients with lymphopenia, 69% showed a reactive lymphocyte population and a lym-
phoplasmacytoid subset, which was uncommon in the peripheral blood of patients with
SARS-CoV-1 (SARS) infections in 2003. No inversion in the CD4+/CD8+ lymphocyte ratio
was observed by flow cytometry; however, functional studies suggest that SARS-CoV-2
may impair the function of CD4+ helper and regulatory T-cells and cause rapid exhaustion
of cytotoxic CD8+ T-cells [8]. In contrast, several reports have shown only 6% of patients
admitted to the hospital for COVID-19 had lymphadenopathies [9]. Immunofluorescence
staining and electron microscopy on six autopsies revealed that SARS-CoV-2 directly in-
fects macrophages in lymph nodes (LNs) [9]. Additionally, palpable lymphadenopathies
have not been reported in COVID-19 patients [9]. These studies suggest that SARS-CoV-2
belongs to a group of viruses that does not normally induce extensive lymphadenopathies.
There have been several factors identified that may contribute to COVID-19-associated
lymphopenia. It has been postulated that since lymphocytes express the ACE2 receptor
on their surface, SARS-CoV-2 can directly infect and lyse lymphocytes [10]. It has also
been suggested that the substantial cytokine activation often seen in severe COVID-19
disease may be associated with lymphoid organ atrophy, which would impact lymphocyte
turnover [10]. Patients who have cancer and therefore are at increased risk for complications
from COVID-19 will also have coexisting lactic acidosis, which may also inhibit lymphocyte
proliferation [16].

4.3. Hematologic Malignancies Put Patients at High Risk of COVID-19 Mortality

Patients with co-existent HMs and COVID-19 are at increased risk of developing
severe and life-threatening infections and have a high mortality risk; they have weakened
immunity due to cancer as well as treatments they may be receiving, and therefore exhibit
reduced response to the COVID-19 vaccines. A case series study found higher fatality rates
in COVID-19 patients with multiple myeloma and related diseases compared to COVID-19
patients without multiple myeloma [17]. Studies have shown that patients with lymphoma
are particularly vulnerable to SARS-CoV-2 infection, possibly due to the antineoplastic
regimens such as BTL or PI3 kinase inhibitors, monocolonal antibodies for CD20, CD30, or
CD38, and CAR-T therapy [18,19]. In this study, it should be noted that there is a bias in
evaluating biomarkers in patients with hematological malignancies such as lymphomas
because the patients may have had longstanding lymphopenia and elevated LDH prior to
COVID-19 disease.
Currently, the American Society of Hematology and the International Myeloma Society
recommend that high-dose chemotherapy and autologous stem cell transplant should
be postponed until the pandemic stabilizes. However, patients with new diagnoses of
HMs are especially vulnerable during the pandemic, and therefore may require prompt
treatment [16,17,20].
 as lymphomas because the patients may have had longstanding lymphopenia and ele-
vated LDH prior to COVID-19 disease.
Currently, the American Society of Hematology and the International Myeloma So-
ciety recommend that high-dose chemotherapy and autologous stem cell transplant
should be postponed until the pandemic stabilizes. However, patients with new diagno-
Hematol. Rep. 2022, 14 233
ses of HMs are especially vulnerable during the pandemic, and therefore may require
prompt treatment [16,17,20].

5. Conclusions
Based on
on our
ourclinical
clinicalobservations
observationsand a series
and of studies,
a series we found
of studies, that severe
we found lym-
that severe
phopenia (<1.3(<1.3
lymphopenia × 10 ×
9 9
/L),10neutrophilia with left-shifted
/L), neutrophilia granulocytes
with left-shifted (>5 × 10(>5
granulocytes 9 9
/L),×acute he-
10 /L),
molysis,
acute HMs, increased
hemolysis, LDH (>225
HMs, increased LDHu/L), andu/L),
(>225 abnormal morphology
and abnormal are usually
morphology observed
are usually
in patients
observed inadmitted to the ICU
patients admitted whoICU
to the have
whorespiratory failure failure
have respiratory requiring intubation,
requiring acute
intubation,
renal failure,
acute and poor
renal failure, and clinical outcome
poor clinical (Figure
outcome 3). These
(Figure findings
3). These were were
findings consistent with
consistent
our literature
with review.
our literature This This
review. should prompt
should providers
prompt to intervene
providers earlyearly
to intervene to improve out-
to improve
outcomes.
comes.

Figure 3.
Figure 3. Summary
Summary of
ofhematologic
hematologiccomplications
complicationsobserved
observedininpatients
patientshospitalized
hospitalizedwith
withCOVID-19
COVID-
infection.
19 infection.

In light
In light of
of these
these findings,
findings, we
we propose
propose two
two important
important additional
additional recommendations
recommendations in
in
the management
the management of of future
future COVID-19
COVID-19 patients:
patients:
1. Early diagnosis and follow-up of DIC by applying the ISTH score, which can deter-
1. Early diagnosis and follow-up of DIC by applying the ISTH score, which can deter-
mine prognosis and guide appropriate critical care support.
mine prognosis and guide appropriate critical care support.
2. Optimization of thromboprophylaxis regimen with LMWH as first-line drug.
2. Optimization of thromboprophylaxis regimen with LMWH as first-line drug.
Author
Author Contributions: M.C.and
Contributions: M.C. andH.L.
H.L.designed
designedthethe study.
study. E.L.E.L. collected
collected rawraw
datadata of study,
of the the study,
car-
carried
ried out data analysis, graphing, and illustration. The first manuscript was written and revised by
out data analysis, graphing, and illustration. The first manuscript was written and revised by
E.L.
E.L. and
and M.C.;
M.C.; E.A.
E.A. and
and J.M.
J.M. provided
provided MRNs
MRNs for for patients who had
patients who had been
been inin the
the ICU
ICU for
for COVID-19.
COVID-19.
All
All authors
authors have
have read
read and
and agreed
agreed to
to the
the published
publishedversion
versionofofthe
themanuscript.
manuscript.
Funding: No
Funding: No funding
funding support
support was
was needed
needed for
for this
this study.
study.
Institutional
Institutional Review
Review Board Statement:The
BoardStatement: Thestudy
studywas
wasconducted
conducted inin
accordance with
accordance thethe
with Declaration
Declara-
of Helsinki,
tion and approved
of Helsinki, by theby
and approved Institutional Review
the Institutional Board Board
Review of the University of Texas
of the University ofSouthwestern
Texas South-
Medical
western Center
Medical(STU 122013-023).
Center (STU 122013-023).
Informed
Informed Consent Statement: The
Consent Statement: Thepatient
patientconsent
consentrequirement was
requirement waived
was by by
waived thethe
IRBIRB
as the patient
as the pa-
identifiers were decoded.
tient identifiers were decoded.
Data
Data Availability Statement: Data
Availability Statement: Data available
available on
on request
request from
from the
the authors.
authors.
Acknowledgments: The
Acknowledgments: The authors
authors would
would like
like to
to acknowledge
acknowledge Alagar
Alagar R.
R. Muthukumar
Muthukumar for
for his
his help
help in
in
providing
providing data
data for
for this
this study.
study.
Conflicts
Conflicts of Interest: The
of Interest: The authors
authors declare
declare no
noconflict
conflictof
ofinterest.
interest.

References
1. WHO Announces COVID-19 Outbreak a Pandemic. Available online: www.euro.who.int/en/health-topics/health-emergencies/
coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic (accessed on 31 May 2021).
2. Al-Saadi, E.A.; Abdulnabi, M.A. Hematological changes associated with COVID-19 infection. J. Clin. Lab. Anal. 2021, 36, e24064.
[CrossRef] [PubMed]
3. Rahman, A.; Niloofa, R.; Jayarajah, U.; De Mel, S.; Abeysuriya, V.; Seneviratne, S.L. Hematological abnormalities in COVID-19: A
narrative review. Am. J. Trop. Med. Hyg. 2021, 104, 1188–1201. [CrossRef] [PubMed]
4. Zhang, Y.; Zeng, X.; Jiao, Y.; Li, Z.; Liu, Q.; Ye, J.; Yang, M. Mechanisms involved in the development of thrombocytopenia in
patients with COVID-19. Thromb. Res. 2020, 193, 110–115. [CrossRef] [PubMed]
5. Johns Hopkins University of Medicine Coronavirus Resource Center. Available online: https://coronavirus.jhu.edu/ (accessed
on 21 January 2022).
6. Asakura, H.; Ogawa, H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int. J. Hematol. 2021,
113, 45–57. [CrossRef] [PubMed]
Hematol. Rep. 2022, 14 234

7. Henry, B.M.; De Oliveira, M.H.S.; Benoit, S.; Plebani, M.; Lippi, G. Hematologic, biochemical and immune biomarker abnormalities
associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis. Clin. Chem. Lab. Med.
(CCLM) 2020, 58, 1021–1028. [CrossRef] [PubMed]
8. Rahi, M.S.; Jindal, V.; Reyes, S.P.; Gunasekaran, K.; Gupta, R.; Jaiyesimi, I. Hematologic disorders associated with COVID-19: A
review. Ann. Hematol. 2021, 100, 309–320. [CrossRef] [PubMed]
9. Zhao, Q.; Meng, M.; Kumar, R.; Wu, Y.; Huang, J.; Deng, Y.; Weng, Z.; Yang, L. Lymphopenia is associated with severe coronavirus
disease 2019 (COVID-19) infections: A systemic review and meta-analysis. Int. J. Infect. Dis. 2020, 96, 131–135. [CrossRef]
[PubMed]
10. Terpos, E.; Ntanasis-Stathopoulos, I.; Elalamy, I.; Kastritis, E.; Sergentanis, T.N.; Politou, M.; Psaltopoulou, T.; Gerotziafas, G.;
Dimopoulos, M.A. Hematological findings and complications of COVID-19. Am. J. Hematol. 2020, 95, 834–847. [CrossRef]
[PubMed]
11. Agbuduwe, C.; Basu, S. Haematological manifestations of COVID-19: From cytopenia to coagulopathy. Eur. J. Haematol. 2020,
105, 540–546. [CrossRef] [PubMed]
12. Yip, C.Y.C.; Yap, E.S.; De Mel, S.; Teo, W.Z.Y.; Lee, C.T.; Kan, S.; Lee, M.C.C.; Loh, W.N.H.; Lim, E.L.; Lee, S.Y. Temporal changes
in immune blood cell parameters in COVID-19 infection and recovery from severe infection. Br. J. Haematol. 2020, 190, 33–36.
[CrossRef] [PubMed]
13. Connors, J.M.; Levy, J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020, 135, 2033–2040.
[CrossRef] [PubMed]
14. Wool, G.D.; Miller, J.L. The impact of COVID-19 disease on platelets and coagulation. Pathobiology 2021, 88, 15–27. [CrossRef]
[PubMed]
15. Maquet, J.; Lafaurie, M.; Sommet, A.; Moulis, G. Thrombocytopenia is independently associated with poor outcome in patients
hospitalized for COVID-19. Br. J. Haematol. 2020, 190, e276–e279. [CrossRef]
16. Vijenthira, A.; Gong, I.Y.; Fox, T.A.; Booth, S.; Cook, G.; Fattizzo, B.; Martín-Moro, F.; Razanamahery, J.; Riches, J.C.; Zwicker,
J.; et al. Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377
patients. Blood 2020, 136, 2881–2892. [CrossRef]
17. Chari, A.; Samur, M.K.; Martinez-Lopez, J.; Cook, G.; Biran, N.; Yong, K.; Hungria, V.; Engelhardt, M.; Gay, F.; García Feria, A.;
et al. Clinical features associated with COVID-19 outcome in multiple myeloma: First results from the International Myeloma
Society data set. Blood 2020, 136, 3033–3040. [CrossRef]
18. Pagano, L.; Salmanton-García, J.; Marchesi, F.; Corradini, P.; Hoenigl, M.; Klimko, N.; Koehler, P.; Pagliuca, A.; Passamonti, F.;
Verga, L.; et al. COVID-19 infection in adult patients with hematological malignancies: A European Hematology Association
Survey (EPICOVIDEHA). J. Hematol. Oncol. 2021, 14, 168. [CrossRef] [PubMed]
19. Yigenoglu, T.N.; Ata, N.; Altuntas, F.; Bascı, S.; Dal, M.S.; Korkmaz, S.; Namdaroglu, S.; Basturk, A.; Hacıbekiroglu, T.; Dogu,
M.H.; et al. The outcome of COVID-19 in patients with hematological malignancy. J. Med. Virol. 2021, 93, 1099–1104. [CrossRef]
[PubMed]
20. Cattaneo, C.; Daffini, R.; Pagani, C.; Salvetti, M.; Mancini, V.; Borlenghi, E.; D’Adda, M.; Oberti, M.; Paini, A.; De Ciuceis, C.; et al.
Clinical characteristics and risk factors for mortality in hematologic patients affected by COVID-19. Cancer 2020, 126, 5069–5076.
[CrossRef] [PubMed]